Epinephrine deficiency results in intact glucose counter-regulation, severe hepatic steatosis and possible defective autophagy in fasting mice

    Authors

    R. I. Sharara-Chami; Y. J. Zhou; S. Ebert; K. Pacak; U. Ozcan;J. A. Majzoub

    Comments

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    Abbreviated Journal Title

    Int. J. Biochem. Cell Biol.

    Keywords

    Brown adipose tissue; Epinephrine; Autophagy; Fasting; Steatosis; Metabolism; ADRENERGIC-MECHANISMS; GLYCEMIC THRESHOLDS; CELLULAR AUTOPHAGY; INSULIN-RESISTANCE; RAT LIVER; GLUCAGON; DISEASE; HUMANS; ALPHA; COUNTERREGULATION; Biochemistry & Molecular Biology; Cell Biology

    Abstract

    Epinephrine is one of the major hormones involved in glucose counter-regulation and gluconeogenesis. However, little is known about its importance in energy homeostasis during fasting. Our objective is to study the specific role of epinephrine in glucose and lipid metabolism during starvation. In our experiment, we subject regular mice and epinephrine-deficient mice to a 48-h fast then we evaluate the different metabolic responses to fasting. Our results show that epinephrine is not required for glucose counter-regulation: epinephrine-deficient mice maintain their blood glucose at normal fasting levels via glycogenolysis and gluconeogenesis, with normal fasting-induced changes in the peroxisomal activators: peroxisome proliferator activated receptor gamma coactivator alpha (PGC-1 alpha), fibroblast growth factor 21 (FGF-21), peroxisome proliferator activated receptor alpha (PPAR-alpha), and sterol regulatory element binding protein (SREBP-1c). However, fasted epinephrine-deficient mice develop severe ketosis and hepatic steatosis, with evidence for inhibition of hepatic autophagy, a process that normally provides essential energy via degradation of hepatic triglycerides during starvation. We conclude that, during fasting, epinephrine is not required for glucose homeostasis, lipolysis or ketogenesis. Epinephrine may have an essential role in lipid handling, possibly via an autophagy-dependent mechanism. (C) 2012 Elsevier Ltd. All rights reserved.

    Journal Title

    International Journal of Biochemistry & Cell Biology

    Volume

    44

    Issue/Number

    6

    Publication Date

    1-1-2012

    Document Type

    Article

    Language

    English

    First Page

    905

    Last Page

    913

    WOS Identifier

    WOS:000304490700013

    ISSN

    1357-2725

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